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Primary lateral sclerosis, adult, 1(PLSA; PLSA1)

MedGen UID:
369357
•Concept ID:
C1968845
•
Disease or Syndrome
Synonyms: PLS, ADULT; PLSA1
 
Monarch Initiative: MONDO:0012708
OMIM®: 611637

Definition

Although primary lateral sclerosis (PLS) is similar to amyotrophic lateral sclerosis (ALS; 105400), they are considered to be clinically distinct progressive paralytic neurodegenerative disorders. Following a period of diagnostic confusion, the clinical distinction between ALS and PLS became clear and diagnostic criteria were established (Pringle et al., 1992). PLS is characterized by degeneration of the upper motor neurons and the corticospinal and corticobulbar tracts, whereas ALS is a more severe disorder characterized by degeneration of both the upper and lower motor neurons. See 606353 for autosomal recessive juvenile-onset PLS, which is caused by mutations in the ALS2 gene (606352). [from OMIM]

Clinical features

From HPO
Dysphagia
MedGen UID:
41440
•Concept ID:
C0011168
•
Disease or Syndrome
Difficulty in swallowing.
See: Feature record | Search on this feature
Babinski sign
MedGen UID:
19708
•Concept ID:
C0034935
•
Finding
Upturning of the big toe (and sometimes fanning of the other toes) in response to stimulation of the sole of the foot. If the Babinski sign is present it can indicate damage to the corticospinal tract.
See: Feature record | Search on this feature
Hyperreflexia
MedGen UID:
57738
•Concept ID:
C0151889
•
Finding
Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles.
See: Feature record | Search on this feature
Spastic gait
MedGen UID:
115907
•Concept ID:
C0231687
•
Finding
Spasticity is manifested by increased stretch reflex which is intensified with movement velocity. This results in excessive and inappropriate muscle activation which can contribute to muscle hypertonia. Spastic gait is characterized by manifestations such as muscle hypertonia, stiff knee, and circumduction of the leg.
See: Feature record | Search on this feature
Spastic dysarthria
MedGen UID:
105312
•Concept ID:
C0454596
•
Finding
A type of dysarthria related to bilateral damage of the upper motor neuron tracts of the pyramidal and extra- pyramidal tracts. Speech of affected individuals is slow, effortful, and has a harsh vocal quality.
See: Feature record | Search on this feature
Spastic tetraparesis
MedGen UID:
658719
•Concept ID:
C0575059
•
Disease or Syndrome
Spastic weakness affecting all four limbs.
See: Feature record | Search on this feature
Abnormal upper motor neuron morphology
MedGen UID:
871241
•Concept ID:
C4025723
•
Anatomical Abnormality
Any structural anomaly that affects the upper motor neuron.
See: Feature record | Search on this feature
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Professional guidelines

PubMed

Management of Spinal Muscular Atrophy in the Adult Population.
Rad N, Cai H, Weiss MD
Muscle Nerve 2022 May;65(5):498-507. Epub 2022 Feb 26 doi: 10.1002/mus.27519. PMID: 35218574
Advances in Treatment of Spinal Muscular Atrophy - New Phenotypes, New Challenges, New Implications for Care.
Schorling DC, Pechmann A, Kirschner J
J Neuromuscul Dis 2020;7(1):1-13. doi: 10.3233/JND-190424. PMID: 31707373Free PMC Article
Neuromuscular diseases: Diagnosis and management.
Mary P, Servais L, Vialle R
Orthop Traumatol Surg Res 2018 Feb;104(1S):S89-S95. Epub 2017 Nov 28 doi: 10.1016/j.otsr.2017.04.019. PMID: 29196274

Recent clinical studies

Etiology

Motoneuron Diseases.
Lotti F, Przedborski S
Adv Neurobiol 2022;28:323-352. doi: 10.1007/978-3-031-07167-6_13. PMID: 36066831
Prognosis for patients with amyotrophic lateral sclerosis: development and validation of a personalised prediction model.
Westeneng HJ, Debray TPA, Visser AE, van Eijk RPA, Rooney JPK, Calvo A, Martin S, McDermott CJ, Thompson AG, Pinto S, Kobeleva X, Rosenbohm A, Stubendorff B, Sommer H, Middelkoop BM, Dekker AM, van Vugt JJFA, van Rheenen W, Vajda A, Heverin M, Kazoka M, Hollinger H, Gromicho M, Körner S, Ringer TM, Rödiger A, Gunkel A, Shaw CE, Bredenoord AL, van Es MA, Corcia P, Couratier P, Weber M, Grosskreutz J, Ludolph AC, Petri S, de Carvalho M, Van Damme P, Talbot K, Turner MR, Shaw PJ, Al-Chalabi A, Chiò A, Hardiman O, Moons KGM, Veldink JH, van den Berg LH
Lancet Neurol 2018 May;17(5):423-433. Epub 2018 Mar 26 doi: 10.1016/S1474-4422(18)30089-9. PMID: 29598923
The epidemiology of amyotrophic lateral sclerosis.
Talbott EO, Malek AM, Lacomis D
Handb Clin Neurol 2016;138:225-38. doi: 10.1016/B978-0-12-802973-2.00013-6. PMID: 27637961
Riluzole for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND).
Miller RG, Mitchell JD, Moore DH
Cochrane Database Syst Rev 2012 Mar 14;2012(3):CD001447. doi: 10.1002/14651858.CD001447.pub3. PMID: 22419278Free PMC Article
Spinal muscular atrophy.
D'Amico A, Mercuri E, Tiziano FD, Bertini E
Orphanet J Rare Dis 2011 Nov 2;6:71. doi: 10.1186/1750-1172-6-71. PMID: 22047105Free PMC Article

Diagnosis

Management of Spinal Muscular Atrophy in the Adult Population.
Rad N, Cai H, Weiss MD
Muscle Nerve 2022 May;65(5):498-507. Epub 2022 Feb 26 doi: 10.1002/mus.27519. PMID: 35218574
Prognosis for patients with amyotrophic lateral sclerosis: development and validation of a personalised prediction model.
Westeneng HJ, Debray TPA, Visser AE, van Eijk RPA, Rooney JPK, Calvo A, Martin S, McDermott CJ, Thompson AG, Pinto S, Kobeleva X, Rosenbohm A, Stubendorff B, Sommer H, Middelkoop BM, Dekker AM, van Vugt JJFA, van Rheenen W, Vajda A, Heverin M, Kazoka M, Hollinger H, Gromicho M, Körner S, Ringer TM, Rödiger A, Gunkel A, Shaw CE, Bredenoord AL, van Es MA, Corcia P, Couratier P, Weber M, Grosskreutz J, Ludolph AC, Petri S, de Carvalho M, Van Damme P, Talbot K, Turner MR, Shaw PJ, Al-Chalabi A, Chiò A, Hardiman O, Moons KGM, Veldink JH, van den Berg LH
Lancet Neurol 2018 May;17(5):423-433. Epub 2018 Mar 26 doi: 10.1016/S1474-4422(18)30089-9. PMID: 29598923
The epidemiology of amyotrophic lateral sclerosis.
Talbott EO, Malek AM, Lacomis D
Handb Clin Neurol 2016;138:225-38. doi: 10.1016/B978-0-12-802973-2.00013-6. PMID: 27637961
Spinal muscular atrophy.
D'Amico A, Mercuri E, Tiziano FD, Bertini E
Orphanet J Rare Dis 2011 Nov 2;6:71. doi: 10.1186/1750-1172-6-71. PMID: 22047105Free PMC Article
Amyotrophic lateral sclerosis.
Wijesekera LC, Leigh PN
Orphanet J Rare Dis 2009 Feb 3;4:3. doi: 10.1186/1750-1172-4-3. PMID: 19192301Free PMC Article

Therapy

Trial of Antisense Oligonucleotide Tofersen for SOD1 ALS.
Miller TM, Cudkowicz ME, Genge A, Shaw PJ, Sobue G, Bucelli RC, Chiò A, Van Damme P, Ludolph AC, Glass JD, Andrews JA, Babu S, Benatar M, McDermott CJ, Cochrane T, Chary S, Chew S, Zhu H, Wu F, Nestorov I, Graham D, Sun P, McNeill M, Fanning L, Ferguson TA, Fradette S; VALOR and OLE Working Group
N Engl J Med 2022 Sep 22;387(12):1099-1110. doi: 10.1056/NEJMoa2204705. PMID: 36129998
Efficacy and Safety of Ultrahigh-Dose Methylcobalamin in Early-Stage Amyotrophic Lateral Sclerosis: A Randomized Clinical Trial.
Oki R, Izumi Y, Fujita K, Miyamoto R, Nodera H, Sato Y, Sakaguchi S, Nokihara H, Kanai K, Tsunemi T, Hattori N, Hatanaka Y, Sonoo M, Atsuta N, Sobue G, Shimizu T, Shibuya K, Ikeda K, Kano O, Nishinaka K, Kojima Y, Oda M, Komai K, Kikuchi H, Kohara N, Urushitani M, Nakayama Y, Ito H, Nagai M, Nishiyama K, Kuzume D, Shimohama S, Shimohata T, Abe K, Ishihara T, Onodera O, Isose S, Araki N, Morita M, Noda K, Toda T, Maruyama H, Furuya H, Teramukai S, Kagimura T, Noma K, Yanagawa H, Kuwabara S, Kaji R; Japan Early-Stage Trial of Ultrahigh-Dose Methylcobalamin for ALS (JETALS) Collaborators
JAMA Neurol 2022 Jun 1;79(6):575-583. doi: 10.1001/jamaneurol.2022.0901. PMID: 35532908Free PMC Article
Safety and Effectiveness of Long-term Intravenous Administration of Edaravone for Treatment of Patients With Amyotrophic Lateral Sclerosis.
Witzel S, Maier A, Steinbach R, Grosskreutz J, Koch JC, Sarikidi A, Petri S, Günther R, Wolf J, Hermann A, Prudlo J, Cordts I, Lingor P, Löscher WN, Kohl Z, Hagenacker T, Ruckes C, Koch B, Spittel S, Günther K, Michels S, Dorst J, Meyer T, Ludolph AC; German Motor Neuron Disease Network (MND-NET)
JAMA Neurol 2022 Feb 1;79(2):121-130. doi: 10.1001/jamaneurol.2021.4893. PMID: 35006266Free PMC Article
Magnesium for skeletal muscle cramps.
Garrison SR, Korownyk CS, Kolber MR, Allan GM, Musini VM, Sekhon RK, Dugré N
Cochrane Database Syst Rev 2020 Sep 21;9(9):CD009402. doi: 10.1002/14651858.CD009402.pub3. PMID: 32956536Free PMC Article
Trial of Sodium Phenylbutyrate-Taurursodiol for Amyotrophic Lateral Sclerosis.
Paganoni S, Macklin EA, Hendrix S, Berry JD, Elliott MA, Maiser S, Karam C, Caress JB, Owegi MA, Quick A, Wymer J, Goutman SA, Heitzman D, Heiman-Patterson T, Jackson CE, Quinn C, Rothstein JD, Kasarskis EJ, Katz J, Jenkins L, Ladha S, Miller TM, Scelsa SN, Vu TH, Fournier CN, Glass JD, Johnson KM, Swenson A, Goyal NA, Pattee GL, Andres PL, Babu S, Chase M, Dagostino D, Dickson SP, Ellison N, Hall M, Hendrix K, Kittle G, McGovern M, Ostrow J, Pothier L, Randall R, Shefner JM, Sherman AV, Tustison E, Vigneswaran P, Walker J, Yu H, Chan J, Wittes J, Cohen J, Klee J, Leslie K, Tanzi RE, Gilbert W, Yeramian PD, Schoenfeld D, Cudkowicz ME
N Engl J Med 2020 Sep 3;383(10):919-930. doi: 10.1056/NEJMoa1916945. PMID: 32877582Free PMC Article

Prognosis

Prognosis for patients with amyotrophic lateral sclerosis: development and validation of a personalised prediction model.
Westeneng HJ, Debray TPA, Visser AE, van Eijk RPA, Rooney JPK, Calvo A, Martin S, McDermott CJ, Thompson AG, Pinto S, Kobeleva X, Rosenbohm A, Stubendorff B, Sommer H, Middelkoop BM, Dekker AM, van Vugt JJFA, van Rheenen W, Vajda A, Heverin M, Kazoka M, Hollinger H, Gromicho M, Körner S, Ringer TM, Rödiger A, Gunkel A, Shaw CE, Bredenoord AL, van Es MA, Corcia P, Couratier P, Weber M, Grosskreutz J, Ludolph AC, Petri S, de Carvalho M, Van Damme P, Talbot K, Turner MR, Shaw PJ, Al-Chalabi A, Chiò A, Hardiman O, Moons KGM, Veldink JH, van den Berg LH
Lancet Neurol 2018 May;17(5):423-433. Epub 2018 Mar 26 doi: 10.1016/S1474-4422(18)30089-9. PMID: 29598923
Prevalence, incidence and carrier frequency of 5q-linked spinal muscular atrophy - a literature review.
Verhaart IEC, Robertson A, Wilson IJ, Aartsma-Rus A, Cameron S, Jones CC, Cook SF, Lochmüller H
Orphanet J Rare Dis 2017 Jul 4;12(1):124. doi: 10.1186/s13023-017-0671-8. PMID: 28676062Free PMC Article
Confirmatory double-blind, parallel-group, placebo-controlled study of efficacy and safety of edaravone (MCI-186) in amyotrophic lateral sclerosis patients.
Abe K, Itoyama Y, Sobue G, Tsuji S, Aoki M, Doyu M, Hamada C, Kondo K, Yoneoka T, Akimoto M, Yoshino H; Edaravone ALS Study Group
Amyotroph Lateral Scler Frontotemporal Degener 2014 Dec;15(7-8):610-7. Epub 2014 Oct 6 doi: 10.3109/21678421.2014.959024. PMID: 25286015Free PMC Article
Spinal muscular atrophy.
D'Amico A, Mercuri E, Tiziano FD, Bertini E
Orphanet J Rare Dis 2011 Nov 2;6:71. doi: 10.1186/1750-1172-6-71. PMID: 22047105Free PMC Article
Amyotrophic lateral sclerosis.
Wijesekera LC, Leigh PN
Orphanet J Rare Dis 2009 Feb 3;4:3. doi: 10.1186/1750-1172-4-3. PMID: 19192301Free PMC Article

Clinical prediction guides

Trial of Antisense Oligonucleotide Tofersen for SOD1 ALS.
Miller TM, Cudkowicz ME, Genge A, Shaw PJ, Sobue G, Bucelli RC, Chiò A, Van Damme P, Ludolph AC, Glass JD, Andrews JA, Babu S, Benatar M, McDermott CJ, Cochrane T, Chary S, Chew S, Zhu H, Wu F, Nestorov I, Graham D, Sun P, McNeill M, Fanning L, Ferguson TA, Fradette S; VALOR and OLE Working Group
N Engl J Med 2022 Sep 22;387(12):1099-1110. doi: 10.1056/NEJMoa2204705. PMID: 36129998
Efficacy and Safety of Ultrahigh-Dose Methylcobalamin in Early-Stage Amyotrophic Lateral Sclerosis: A Randomized Clinical Trial.
Oki R, Izumi Y, Fujita K, Miyamoto R, Nodera H, Sato Y, Sakaguchi S, Nokihara H, Kanai K, Tsunemi T, Hattori N, Hatanaka Y, Sonoo M, Atsuta N, Sobue G, Shimizu T, Shibuya K, Ikeda K, Kano O, Nishinaka K, Kojima Y, Oda M, Komai K, Kikuchi H, Kohara N, Urushitani M, Nakayama Y, Ito H, Nagai M, Nishiyama K, Kuzume D, Shimohama S, Shimohata T, Abe K, Ishihara T, Onodera O, Isose S, Araki N, Morita M, Noda K, Toda T, Maruyama H, Furuya H, Teramukai S, Kagimura T, Noma K, Yanagawa H, Kuwabara S, Kaji R; Japan Early-Stage Trial of Ultrahigh-Dose Methylcobalamin for ALS (JETALS) Collaborators
JAMA Neurol 2022 Jun 1;79(6):575-583. doi: 10.1001/jamaneurol.2022.0901. PMID: 35532908Free PMC Article
Safety and Effectiveness of Long-term Intravenous Administration of Edaravone for Treatment of Patients With Amyotrophic Lateral Sclerosis.
Witzel S, Maier A, Steinbach R, Grosskreutz J, Koch JC, Sarikidi A, Petri S, Günther R, Wolf J, Hermann A, Prudlo J, Cordts I, Lingor P, Löscher WN, Kohl Z, Hagenacker T, Ruckes C, Koch B, Spittel S, Günther K, Michels S, Dorst J, Meyer T, Ludolph AC; German Motor Neuron Disease Network (MND-NET)
JAMA Neurol 2022 Feb 1;79(2):121-130. doi: 10.1001/jamaneurol.2021.4893. PMID: 35006266Free PMC Article
Effects of Exercise in Patients With Amyotrophic Lateral Sclerosis: A Systematic Review and Meta-Analysis.
Meng L, Li X, Li C, Tsang RCC, Chen Y, Ge Y, Gao Q
Am J Phys Med Rehabil 2020 Sep;99(9):801-810. doi: 10.1097/PHM.0000000000001419. PMID: 32452880
Prognosis for patients with amyotrophic lateral sclerosis: development and validation of a personalised prediction model.
Westeneng HJ, Debray TPA, Visser AE, van Eijk RPA, Rooney JPK, Calvo A, Martin S, McDermott CJ, Thompson AG, Pinto S, Kobeleva X, Rosenbohm A, Stubendorff B, Sommer H, Middelkoop BM, Dekker AM, van Vugt JJFA, van Rheenen W, Vajda A, Heverin M, Kazoka M, Hollinger H, Gromicho M, Körner S, Ringer TM, Rödiger A, Gunkel A, Shaw CE, Bredenoord AL, van Es MA, Corcia P, Couratier P, Weber M, Grosskreutz J, Ludolph AC, Petri S, de Carvalho M, Van Damme P, Talbot K, Turner MR, Shaw PJ, Al-Chalabi A, Chiò A, Hardiman O, Moons KGM, Veldink JH, van den Berg LH
Lancet Neurol 2018 May;17(5):423-433. Epub 2018 Mar 26 doi: 10.1016/S1474-4422(18)30089-9. PMID: 29598923

Recent systematic reviews

Causal role of high body mass index in multiple chronic diseases: a systematic review and meta-analysis of Mendelian randomization studies.
Larsson SC, Burgess S
BMC Med 2021 Dec 15;19(1):320. doi: 10.1186/s12916-021-02188-x. PMID: 34906131Free PMC Article
Magnesium for skeletal muscle cramps.
Garrison SR, Korownyk CS, Kolber MR, Allan GM, Musini VM, Sekhon RK, Dugré N
Cochrane Database Syst Rev 2020 Sep 21;9(9):CD009402. doi: 10.1002/14651858.CD009402.pub3. PMID: 32956536Free PMC Article
Effects of Exercise in Patients With Amyotrophic Lateral Sclerosis: A Systematic Review and Meta-Analysis.
Meng L, Li X, Li C, Tsang RCC, Chen Y, Ge Y, Gao Q
Am J Phys Med Rehabil 2020 Sep;99(9):801-810. doi: 10.1097/PHM.0000000000001419. PMID: 32452880
Respiratory muscle training in children and adults with neuromuscular disease.
Silva IS, Pedrosa R, Azevedo IG, Forbes AM, Fregonezi GA, Dourado Junior ME, Lima SR, Ferreira GM
Cochrane Database Syst Rev 2019 Sep 5;9(9):CD011711. doi: 10.1002/14651858.CD011711.pub2. PMID: 31487757Free PMC Article
Riluzole for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND).
Miller RG, Mitchell JD, Moore DH
Cochrane Database Syst Rev 2012 Mar 14;2012(3):CD001447. doi: 10.1002/14651858.CD001447.pub3. PMID: 22419278Free PMC Article

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